纳米MOFs药物载体的制备与性能研究

发布时间：2018-03-23 23:27

本文选题：金属有机骨架材料　切入点：超声-搅拌法　出处：《哈尔滨理工大学》2017年硕士论文

【摘要】：金属有机骨架材料(Metal-Organic Frameworks,MOFs)是由金属离子与有机配体通过自组装过程杂化生成的一类具有周期性多维网状结构的多孔材料,在催化、传感、气体储存和载药等方面均表现出了优异的性能。成为了科研人员研究的热点。特别在载药方面,由于其大的比表面积,以及较好的生物相容性已被科研人员定位良好的药物载体。本文制备了三种生物相容性较好的纳米MOFs药物载体,进而利用后合成修饰对药物载体功能化,实现了药物载体联合载药和潜在主动肿瘤靶向性。本文利用超声-搅拌法及优化反应条件制备了粒径在300 nm以下的纳米ZIF-90材料,利用傅里叶红外光谱(FT-IR)、X-射线粉末衍射(XRD)确定了其结构,扫描电子显微镜(SEM)确定了大小形貌。进而利用ZIF-90配体中醛基与抗肿瘤药物阿霉素(DOX)中氨基进行缩合反应,将DOX修饰在ZIF-90纳米材料表面,利用固体核磁碳谱、FT-IR、热重(TGA)确定了DOX成功修饰。对纳米药物载体DOX@ZIF-90装载和释放抗癌药物5-氟尿嘧啶(5-Fu)进行了研究,该纳米药物载体的装载5-Fu能力最高可达0.572 g/g;由于ZIF-90的p H不稳定性,使得在肿瘤组织处释放时,DOX的释放量为0.45g/g,5-Fu的释放率达到95%以上。并且该药物载体是首个基于MOFs材料实现联合装载两种抗肿瘤药物的载体。通过加热回流搅拌法及优化反应条件制备了纳米PCN-223与纳米MOF-808材料,利用FT-IR、XRD确定了其结构,SEM确定了各自的形貌和大小,进一步利用靶向制剂叶酸(FA)通过配位作用修饰在了PCN-223与MOF-808材料上,利用固体核磁碳谱、FT-IR、TGA和紫外可见光谱(UV-vis)并对其装载和释放抗肿瘤药物5-Fu进行了研究。结果表明FA@PCN-223材料装载5-Fu最高可达0.654 g/g,释放率为80.14%;FA@MOF-808材料装载5-Fu最高可达0.846 g/g,释放率为78.13%。该药物载体是首次通过配位作用实现MOFs材料潜在主动肿瘤靶向药物载体。
[Abstract]:Metal-Organic frameworks (MOFs) is a kind of porous materials with periodic multi-dimensional network structure formed by self-assembly of metal ions and organic ligands. Gas storage and drug loading have shown excellent performance. It has become a hot spot in scientific research. Especially in drug loading, due to its large specific surface area, In this paper, three kinds of nano-scale MOFs drug carriers with good biocompatibility were prepared, and then the drug carriers were functionalized by post-synthetic modification. The drug carrier combined drug loading and potential active tumor targeting were realized. In this paper, nanocrystalline ZIF-90 materials with particle size less than 300nm were prepared by ultrasonic stirring method and optimized reaction conditions. The structure was determined by Fourier transform infrared spectroscopy (FT-IR) and the morphology was determined by scanning electron microscopy (SEM). Furthermore, the condensation reaction of aldehydes in ZIF-90 ligands with amino groups in the anti-tumor drug doxorubicin (DOX) was carried out. DOX was modified on the surface of ZIF-90 nanomaterials. The DOX modification was confirmed by solid nuclear magnetic resonance spectroscopy (FT-IR) and thermogravimetric analysis (TGA). The loading and release of 5-fluorouracil (5-Fu), an anticancer drug, was studied on the nano-drug carrier DOX@ZIF-90. The 5-Fu loading capacity of the nano-drug carrier can be up to 0.572 g / g. Due to the pH instability of ZIF-90, The release rate of dox is more than 95% when released in tumor tissue, and the drug carrier is the first to carry two kinds of antitumor drugs based on MOFs material. Nano PCN-223 and nano MOF-808 materials were prepared under optimized reaction conditions. The morphology and size of the two materials were determined by FT-IR XRD. Furthermore, the PCN-223 and MOF-808 materials were modified by coordination reaction with the targeted preparation folate. The loading and release of antitumor drug 5-Fu were studied by means of solid nuclear magnetic resonance carbon spectroscopy FT-IRGA-TGA and UV-vis-vis spectra. The results show that the maximum loading of 5-Fu in FA@PCN-223 materials can be up to 0.654 g / g, and the release rate is 80.14% FAMOF-808 with 5-Fu loading up to 0.846 g / g, and the release rate is up to 0.846 g / g. The drug carrier is the first potential active tumor targeting drug carrier of MOFs material through coordination.
【学位授予单位】：哈尔滨理工大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：TQ460.1;TB383.1

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